As the base sequences of the human genomes have been decoded, research subjects have been shifted to genome drug discovery and the search and identification of drug discovery targets. Against this background, there are some noticeable reports that non-steroidal anti-inflammatory drugs (NSAIDs) such as sulindac, derivatives thereof, and celecoxib, which have traditionally been used as non-steroidal anti-inflammatory analgesics, also exhibit efficacy in the area of cancers such as familial adenomatous polyposis (FAP) that was not at all anticipated in early days, one of which concerns the identification of a target considered to account for the efficacy of these compounds in the cancer area.
To date, as the mechanism behind this phenomenon, mainly the contribution of cyclooxygenase (COX) (COX1, COX2), which is a specific target for these NSAIDs, has been suggested (see Cancer Research, 57, pp. 2452-2459 (1997)). However, sulindac and certain sulindac derivatives (specifically sulindac sulfone) exhibit only weak inhibitory effect on COX1 and COX2 (see Cancer Research, 57, pp. 2909-2915 (1997)).
Regarding the efficacy for FAP of sulindac derivatives (sulindac sulfone and the like), which have weak activity on COX as described above, and whose involvement in anticancer effect is unlikely, their relation to phosphodiesterase 5 (PDE5) inhibitory effect has been suggested to date, and experiments have been performed at in vitro and in vivo laboratory levels (see Cancer Research, 57, pp. 2452-2459 (1997)). However, something remains insufficient to explain all the anticancer effect of these derivatives in clinical settings, and the elucidation of the true mechanism thereof has been awaited.